Preclinical and clinical research on the discriminative stimulus effects of nicotine.
Preclinical and clinical research on the discriminative stimulus effects of nicotine.
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尼古丁辨别刺激作用的临床前和临床研究。
DOI：
10.1016/j.neuropharm.2020.108063
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发表时间：
2020
影响因子：
4.7
通讯作者：
Perkins,KennethA
中科院分区：
文献类型：
--
作者：
Shoaib,Mohammed;Perkins,KennethA
跨物种，尼古丁可以产生强大的歧视性刺激（DS）的影响，与其他药物的滥用，这一特点已被利用，以促进我们对尼古丁的作用的神经药理学机制的理解。由于尼古丁在支持烟草依赖方面发挥着至关重要的作用，尼古丁DS效应为开发新一代戒烟化合物提供了理想的平台。临床前研究的发现扩展了人类辨别力研究的领域，以客观地评估尼古丁的内感受刺激效应。因此，翻译研究为尼古丁DS研究提供了概念证明，作为评估尼古丁本身主观影响的方法，与吸烟中涉及的非尼古丁刺激分开。最近的低剂量临床研究表明，感知尼古丁的DS效应是必要的，但还不足以使该剂量得到加强。这些措施有助于制定关于建立烟草制品中所含尼古丁的阈值剂量的新策略，然后确定无法区分的亚阈值剂量，因此无法维持强化。临床前和临床尼古丁DS研究的结果可以为旨在规范消费品尼古丁含量的公共卫生政策提供实质性信息，以最大限度地降低依赖风险。本文是“尼古丁神经药理学当代进展”特刊的一部分。
Across species, nicotine can produce robust discriminative stimulus (DS) effects, as with other drugs of abuse, a feature that has been harnessed to advance our understanding on the neuropharmacological mechanisms of nicotine's actions. With the crucial role played by nicotine in supporting tobacco dependence, nicotine DS effects have presented an ideal platform to develop novel generation of smoking cessation compounds. Findings from preclinical strands of research have invigorated the field of human discrimination research to objectively assess nicotine's interoceptive stimulus effects. As such, translation studies provide proof of concept for nicotine DS research as a method to assess the subjective effects of nicotine per se, separate from non-nicotine stimuli involved in smoking. Recent clinical studies with low doses have demonstrated that perceiving nicotine's DS effects is necessary, yet not sufficient, for that dose to be reinforcing. These measures have been instrumental in developing novel strategies with regards to establishing threshold doses of nicotine contained in tobacco products, to then determine subthreshold doses that cannot be discriminated and, therefore, fail to maintain reinforcement. Findings from preclinical and clinical nicotine DS research could substantially inform public health policies aimed at regulating nicotine content of consumer products so that they minimize risks of dependency.This article is part of the special issue on ‘Contemporary Advances in Nicotine Neuropharmacology’.